In FY 2016 we used our humanized mouse model to investigate HIV in several ways. Most importantly, experiments in FY2016 revealed that our TKO-BLT humanized mouse model can be used in long-term studies (up to one year) with ART administered by injections or via an oral route (drugs incorporated into mouse chow). Such mice develop chronic and latent HIV infections. We have demonstrated that HIV viral loads in these mice can be suppressed to levels undetectable by highly sensitive PCR tests for viremia and provirus. Importantly, the mice are extremely sensitive tools for cure studies as mice with undetectable virus relapse with high viremia following withdrawal of ART. The goal of the upcoming year will be to test HIV Cure drugs using this model. Two published studies in 2016 also demonstrated that human alpha interferon subset 14 works much better in vitro and in vivo to suppress HIV than subset 2, which is currently in clinical trials. Further studies combining IFNa14 with ART are underway. Using our humanized mouse model, we also investigated the role of amyloid fibrils from semen-derived peptide (SEVI) in enhancing HIV-1 infectivity in vivo. We confirmed that SEVI enhanced infectivity in vitro but found no enhancement via the rectal route in vivo. These studies bring into question the utility of using SEVI inhibitors as prophylactics.